Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jul;47(7):1805-1814.
doi: 10.1007/s40618-023-02268-0. Epub 2024 Apr 29.

Improved overall survival in patients developing endocrine toxicity during treatment with nivolumab for advanced non-small cell lung cancer in a prospective study

M Albertelli #  1   2 , G Rossi #  3 , E Nazzari  4 , C Genova  5   6 , F Biello  7 , E Rijavec  8 , M G Dal Bello  3 , L Patti  4 , M Tagliamento  5   6 , G Barletta  3 , P Morabito  3 , M Boschetti  9   4 , A Dotto  4 , D Campana  10 , D Ferone  9   4 , F Grossi  8
Affiliations

Improved overall survival in patients developing endocrine toxicity during treatment with nivolumab for advanced non-small cell lung cancer in a prospective study

M Albertelli et al. J Endocrinol Invest. 2024 Jul.

Abstract

Purpose: Immune checkpoint inhibitors (ICPIs) disrupting PD-1/PD-L1 axis have revolutionized the management of advanced non-small cell lung cancer (NSCLC). Some studies identified the development of endocrine toxicity as predictor of better survival in cancer patients treated with ICPIs. The aim of study was to evaluate survival and new onset of immune-related endocrine adverse events (irAEs) in patients treated with nivolumab for advanced NSCLC.

Methods: In a prospective study, 73 patients with previously treated advanced NSCLC received nivolumab in monotherapy. Blood samples were collected at each cycle to monitor thyroid autoimmunity, thyroid, adrenal and somatotroph axes, while thyroid morphology was evaluated by ultrasonography.

Results: An impaired thyroid function was recorded in 23.4% of patients (n = 15). Eight patients developed asymptomatic transient thyrotoxicosis (ATT) evolving to hypothyroidism in 50% of cases. In addition, seven patients developed overt hypothyroidism without ATT and with negative autoantibodies. Patients who developed hypothyroidism proved to have better overall survival (OS) as compared with non-developers at both univariate (p = 0.021) and multivariate analyses (p = 0.023). The survival curve of patients with reduced IGF-I at baseline, or displaying its reduction during the follow-up, showed significantly reduced median survival compared to patients with normal/high IGF-I levels (p = 0.031).

Conclusions: Thyroid function abnormalities are the major irAEs in patients treated with nivolumab, and hypothyroidism onset is associated with prolonged survival. Our findings indicate that the development of hypothyroidism is a positive predictive biomarker of nivolumab antitumor efficacy in patients with NSCLC. Low IGF-I levels could represent a negative prognostic factor during nivolumab therapy.

Keywords: Endocrine toxicity; Hypothyroidism; NSCLC; Nivolumab; Overall survival.

PubMed Disclaimer

Conflict of interest statement

CG received honoraria from Astra Zeneca, Boehringer Ingelheim, Bristol-Myers-Squibb, Merck, Sharp & Dohme, Roche, Sanofi, Takeda, and ThermoFisher. FG received honoraria from Astra Zeneca, Bristol-Myers-Squibb, Merck, Sharp & Dohme, and Roche. The other authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this manuscript.

Figures

Fig. 1
Fig. 1
Survival analysis of patients according to IGF-I levels (p = 0.031)
Fig. 2
Fig. 2
Survival analysis of patients according to development of irreversible hypothyroidism (p = 0.023)
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Cheung YM, Wang W, McGregor B, et al. Associations between immune-related thyroid dysfunction and efficacy of immune checkpoint inhibitors: a systematic review and meta-analysis. Cancer Immunol Immunother. 2022;71(8):1795–1812. doi: 10.1007/s00262-021-03128-7. - DOI - PMC - PubMed
    1. De Miguel M, Calvo E. Clinical challenges of immune checkpoint inhibitors. Cancer Cell. 2020;38(3):326–333. doi: 10.1016/j.ccell.2020.07.004. - DOI - PubMed
    1. Albertelli M, Dotto A, Nista F, et al. Present and future of immunotherapy in neuroendocrine tumors. Rev Endocr Metab Disord. 2021;22(3):615–636. doi: 10.1007/s11154-021-09647-z. - DOI - PMC - PubMed
    1. Melosky B, Juergens R, Hirsh V, et al. Amplifying outcomes: checkpoint inhibitor combinations in first-line non-small cell lung cancer. Oncologist. 2020;25(1):64–77. doi: 10.1634/theoncologist.2019-0027. - DOI - PMC - PubMed
    1. Fanciulli G, Di Molfetta S, Dotto A, et al. Emerging therapies in pheochromocytoma and paraganglioma: immune checkpoint inhibitors in the starting blocks. J Clin Med. 2020;10(1):88. doi: 10.3390/jcm10010088. - DOI - PMC - PubMed

MeSH terms

Substances